Severe breakthrough COVID-19 cases in the SARS-CoV-2 delta (B.1.617.2) variant era.
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ABSTRACT:
SUBMITTER: Wang SY
PROVIDER: S-EPMC8641954 | biostudies-literature | 2022 Jan
REPOSITORIES: biostudies-literature
Publications
Severe breakthrough COVID-19 cases in the SARS-CoV-2 delta (B.1.617.2) variant era.
Wang Stephen Y SY Juthani Prerak V PV Borges Kelly A KA Shallow Marcus K MK Gupta Akash A Price Christina C Won Christine H CH Chun Hyung J HJ
The Lancet. Microbe 20211203 1
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Project description:BackgroundThe SARS-CoV-2 Delta variant (B.1.617.2), first detected in India, has rapidly become the dominant variant in England. Early reports suggest this variant has an increased growth rate suggesting increased transmissibility. This study indirectly assessed differences in transmissibility between the emergent Delta variant compared to the previously dominant Alpha variant (B.1.1.7).MethodsA matched case-control study was conducted to estimate the odds of household transmission (≥ 2 cases within 14 days) for Delta variant index cases compared with Alpha cases. Cases were derived from national surveillance data (March to June 2021). One-to-two matching was undertaken on geographical location of residence, time period of testing and property type, and a multivariable conditional logistic regression model was used for analysis.FindingsIn total 5,976 genomically sequenced index cases in household clusters were matched to 11,952 sporadic index cases (single case within a household). 43.3% (n=2,586) of cases in household clusters were confirmed Delta variant compared to 40.4% (n= 4,824) of sporadic cases. The odds ratio of household transmission was 1.70 among Delta variant cases (95% CI 1.48-1.95, p <0.001) compared to Alpha cases after adjusting for age, sex, ethnicity, index of multiple deprivation (IMD), number of household contacts and vaccination status of index case.InterpretationWe found evidence of increased household transmission of SARS-CoV-2 Delta variant, potentially explaining its success at displacing Alpha variant as the dominant strain in England. With the Delta variant now having been detected in many countries worldwide, the understanding of the transmissibility of this variant is important for informing infection prevention and control policies internationally.
| S-EPMC8552812 | biostudies-literature
Project description:BackgroundThe Delta variant (Pango lineage B.1.617.2) is one of the most significant and aggressive variants of SARS-CoV-2. To the best of our knowledge, this is the first paper specifically studying pulmonary morphopathology in COVID-19 caused by the B.1.617.2 Delta variant.MethodsThe study included 10 deceased patients (40-83 years) with the COVID-19 Delta variant. The necrotic lung fragments were obtained either by biopsy (six cases) or autopsy (four cases). Tissue samples were subjected to virology analysis for identification of the SARS-CoV-2 variant, histopathology, and immunohistochemistry (anti-SARS coronavirus mouse anti-virus antibody).ResultsVirology analysis identified B.1.617.2 through genetic sequencing in eight cases, and in two cases, specific mutations of B.1.617.2 were identified. Macroscopically, in all autopsied cases, the lung had a particular appearance, purple in color, with increased consistency on palpation and abolished crepitations. Histopathologically, the most frequently observed lesions were acute pulmonary edema (70%) and diffuse alveolar damage at different stages. The immunohistochemical examination was positive for proteins of SARS-CoV-2 in 60% of cases on alveolocytes and in endothelial cells.ConclusionsThe histopathological lung findings in the B.1.617.2 Delta variant are similar to those previously described in COVID-19. Spike protein-binding antibodies were identified immunohistochemically both on alveolocytes and in the endothelial cells, showing the potential of indirect damage from thrombosis.
| S-EPMC9961426 | biostudies-literature
Project description: Not available
| S-EPMC8354568 | biostudies-literature
Project description:The B.1.617.2 (Delta) variant of concern is causing a new wave of infections in many countries. In order to better understand the changes of the SARS-CoV-2 mutation at the genetic level, we selected six mutations in the S region of the Delta variant compared with the native SARS-CoV-2 and get the conductance information of these six short RNA oligonucleotides groups by construct RNA: DNA hybrids. The electronic characteristics are investigated by the combination of density functional theory and non-equilibrium Green's function formulation with decoherence. We found that conductance is very sensitive to small changes in virus sequence. Among the 6 mutations in the Delta S region, D950N shows the largest change in relative conductance, reaching a surprising 4104.75%. These results provide new insights into the Delta variant from the perspective of its electrical properties. This may be a new method to distinguish virus variation and possess great research prospects.
| S-EPMC9364919 | biostudies-literature
Project description:The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.
| S-EPMC8566220 | biostudies-literature
Project description:Competition assays were conducted in vitro and in vivo to examine how the Delta (B.1.617.2) variant displaced the prototype Washington/1/2020 (WA/1) strain. While WA/1 virus exhibited a moderately increased proportion compared to that in the inoculum following co-infection in human respiratory cells, Delta variant possessed a substantial in vivo fitness advantage as this virus becoming predominant in both inoculated and contact animals. This work identifies critical traits of the Delta variant that likely played a role in it becoming a dominant variant and highlights the necessities of employing multiple model systems to assess the fitness of newly emerged SARS-CoV-2 variants.
| S-EPMC10073010 | biostudies-literature
Project description:For a more precise understanding of the course of the pathological process in patients with severe COVID-19, it is necessary to continue the search for factors that affect the course of the pathological process and the possibility of a favorable outcome in critically ill patients. Comparative analysis of the transcriptome of peripheral blood mononuclear cell (PBMCs) in patients with a severe clinical course of COVID-19 caused by the SARS-CoV2 Delta strain revealed a number of differentially expressed genes that distinguish patients with different clinical outcomes (survivors vs. nonsurvivors) in the period of 30 days after admission to the hospital. resuscitation. Most of them are associated with the "negative regulation of viral process" and "negative regulation of immune response" clusters. Moreover, in surviving patients, there is increased expression of the key genes C1QB, C1QA, ISG15, SERPING1, VSIG4, KLRD1, TRPM4, and HFE incorporated in these clusters. Among these key genes, the ISG15 gene, which links several clusters of GO enrichments and encodes an interferon-induced ubiquitin-like protein, deserves special attention. An increase in the level of expression of the ISG15 protein may play a role in response to the expression of the viral protease PLpro, but the exact role of this protein in the prevention of negative disease outcomes is not yet clear.
2025-05-15 | GSE272392 | GEO
Project description:Background: Post infection immunity and post vaccination immunity both confer protection against COVID-19. However, there have been many whole genome sequencing proven reinfections and breakthrough infections. Both are most often mild and caused by Variants of Concern (VOC). Methods: The patient in our study underwent serial COVID-19 RT-PCR, blood tests for serology, acute phase reactants, and chest imaging as part of clinical care. We interviewed the patient for clinical history and retrieved reports and case papers. We retrieved stored RT-PCR positive samples for whole genome sequencing (WGS) of SARS-CoV-2 from the patient's breakthrough infections and the presumed index case. Findings: The patient had three RT-PCR confirmed SARS-CoV-2 infections. Two breakthrough infections occurred in quick succession with the first over 3 weeks after complete vaccination with COVISHIELD and despite post-vaccination seroconversion. The first breakthrough infection was due to the Alpha variant and the second due to the Delta variant. The Delta variant infection resulted in hypoxia, hospitalization, and illness lasting seven weeks. Serial serology, acute phase reactants, and chest imaging supported WGS in establishing distinct episodes of infection. WGS established a fully vaccinated family member as the index case. Interpretation: The patient had an Alpha variant breakthrough infection despite past infection, complete vaccination, and seroconversion. Despite boosting after this infection, the patient subsequently had a severe Delta variant breakthrough infection. This was also a WGS proven reinfection and, therefore, a case of breakthrough reinfection. The patient acquired the infection from a fully vaccinated family member.
| S-EPMC8418387 | biostudies-literature
Project description:ImportanceThe Delta variant (B.1.617.2) is estimated to be more transmissible than previous strains of SARS-CoV-2, especially among children and adolescents. However, to our knowledge, there are no reports confirming this to date.ObjectiveTo gain a better understanding of the association of age with susceptibility to the Delta variant of SARS-CoV-2.Design, setting, and participantsThis decision analytic model used an age-structured compartmental model using the terms symptom onset (S), exposure (E), infectious (I), and quarantine (Q) (SEIQ) to estimate the age-specific force of infection, combining age-specific contact matrices and observed distribution of periods between each stage of infection (E to I [ie, latent period], I given S, and S to Q [ie, diagnostic delay]) developed in a previous contact tracing study. A bayesian inference method was used to estimate the age-specific force of infection (S to E) and, accordingly, age-specific susceptibility. The age-specific susceptibility during the third wave (ie, before Delta, from October 15 to December 22, 2020, when the COVID-19 vaccination campaign was not yet launched) and the fourth wave (ie, the Delta-driven wave, from June 27 to August 21, 2021) in Korea were compared. As vaccine uptake increased, individuals who were vaccinated were excluded from the susceptible population in accordance with vaccine effectiveness against the Delta variant. This nationwide epidemiologic study included individuals who were diagnosed with COVID-19 during the study period in Korea. Data were analyzed from September to November 2021.ExposuresAge group during the third wave (ie, before Delta) and fourth wave (ie, Delta-driven) of the COVID-19 pandemic in South Korea.Main outcomes and measuresAge-specific susceptibility during the third and fourth waves was estimated.ResultsAmong 106 866 confirmed COVID-19 infections (including 26 597 infections and 80 269 infections during the third and fourth waves of COVID-19 in Korea, respectively), a significant difference in age-specific susceptibility to the Delta vs pre-Delta variant was found in the younger age group. After adjustment for contact pattern and vaccination status, the increase in susceptibility to the Delta vs pre-Delta variant was estimated to be highest in the group aged 10 to 15 years, approximately doubling (1.92-fold increase [95% CI, 1.86-fold to 1.98-fold]), whereas in the group aged 50 years or more, susceptibility to the Delta vs pre-Delta variant remained stable at an approximately 1-fold change (eg, among individuals aged 50-55 years: 0.997-fold [95% CI, 0.989-fold to 1.001-fold).Conclusions and relevanceIn this study, the Delta variant of SARS-CoV-2 was estimated to propagate more easily among children and adolescents than pre-Delta strains, even after adjusting for contact pattern and vaccination status.
| S-EPMC8933737 | biostudies-literature
Project description:The emergence of the B.1.617.2 (Delta) variant of the severe acute syndrome coronavirus (SARS-CoV-2) that emerged in 2019 (COVID-19), resulted in a surge of cases in India and has expanded and been detected across the world, including in the United States. The B.1.617.2 (Delta) variant has been seen to be twice more transmissible coupled with potential increases in disease severity and immune escape. As a result, case numbers and hospitalisations are once again on the rise in the USA. On 16 July 2021, the Centers for Disease Control and Prevention (CDC) reported a 7-day average 69.3% increase in new cases and a 35% increase in hospitalisations. Although the gold standard for SARS-CoV-2 variants identification remains genomic sequencing, this approach is not accessible to many clinical laboratories. The main goal of this study was to validate and implement the detection of the B.1.617.2 (Delta) variant utilising an open reverse transcription polymerase chain reaction (RT-PCR) platform by explicitly detecting the S-gene target failure (SGTF) corresponding to the deletion of two amino acids (ΔE156/ΔF157) characteristic of B.1.617.2 (Delta) variant. This approach was conceived as a rapid screening of B.1.617.2 (Delta) variant in conjunction with CDC's recommended N1 (nucleocapsid gene), N2, and RP (human RNase P) genes, as a pre-screening tool prior to viral genomic sequencing. We assessed 4,937 samples from 5 July to 5 September 2021. We identified the B.1.617.2 (Delta) variant in 435 of 495 positive samples (87.8%); the additional positive samples (7 samples, 1.4%) were found to belong to the B.1.1.7 (Alpha, UK) lineage and the remaining 53 samples (10.7%) were reported as 'other' lineages. Whole genome sequencing of 46 randomly selected samples validated the strains identified as positive and negative for the B.1.617.2 (Delta) variant and confirmed the S gene deletion in addition to B.1.617.2 characteristic mutations including L452R, T478K, P681R and D950N located in the spike protein. This modality has been used as routine testing at the Riverside University System Health (RUHS) Medical Center as a method for detection of B.1.617.2 (Delta) to pre-screen samples before genome sequencing. The assay can be easily implemented in clinical laboratories, most notably those with limited economic resources and access to genomic platforms.
| S-EPMC8801325 | biostudies-literature